Influenza (seasonal, pandemic, and avian) vaccine program

The GVI adjuvant enhances seasonal flu vaccine by a factor of 20

The promising activity of the GVI adjuvant and many of its characteristics have been demonstrated in mice with an inactivated vaccine for seasonal influenza (H1N1). Collaborating with the University of California at Davis, we have also shown a strong adjuvant effect in monkeys using a commercially available Sanofi H1N1 vaccine, Fluzone™. Systemic antibodies were increased by a factor of 20 in the monkeys that received Fluzone™ plus GVI adjuvant compared to animals receiving Fluzone™ alone, and the responses were uniformly high among the individual animals in the adjuvant group. Moreover, protective levels of antibody were achieved with a single inoculation in 5 out of 6 animals compared to 1 out of 6 in the Fluzone™ only group.

Cellular immunity and mucosal immunity were demonstrated in the GVI adjuvant group but not in the animals receiving vaccine alone. Even after two inoculations, comparison between the Fluzone™ only group and unvaccinated animals showed no significant difference in terms of protection, as measured by influenza virus titers in the lung after challenge. Protection in the group that received Fluzone™ plus GVI adjuvant was significantly better than that observed in either the Fluzone™ only group or the unvaccinated group.

The GVI adjuvant shown to significantly boost efficacy of the avian flu vaccine

In the late 1990s and early 2000s, outbreaks of disease from the highly pathogenic avian influenza A H5N1 virus occurred, with human fatality rates as high as 50% in some instances. While human-to-human transmission of H5N1 has been very rare and unsustained, H5N1 virus infections among poultry have become endemic in certain regions and still cause sporadic human infections from direct contact with infected poultry.

The federal government has stockpiled an avian flu (H5N1) vaccine candidate manufactured under cGMP by Sanofi. However, the ability of this vaccine alone to induce protective immune responses in humans is poor, and the corresponding need for an effective adjuvant is clear.

We have tested the Sanofi H5N1 vaccine in mice with and without the GVI adjuvant, collaborating with scientists at St. Jude Childrens Research Hospital. Without the GVI adjuvant, there is little or no detectable response when measuring hemagglutination inhibition (HI) antibodies. HI antibodies are thought to correlate with protection in humans. With the GVI adjuvant, we demonstrated very strong HI responses. Moreover, cellular immunity and mucosal immunity were detected, and the responses were potent across a broad range of distantly related H5N1 isolates. Protection against challenge with virulent H5N1 was virtually complete with reductions of 3 to 4 orders of magnitude in challenge virus replication in the lung.

We are currently developing a process for GMP-like manufacture of the GVI adjuvant in collaboration with a group at Colorado State University. This material will be evaluated in GLP toxicology tests by a third party contract research organization (CRO), and will be used for further monkey trials at the University of California at Davis. We hope to proceed to cGMP manufacture and a Phase I clinical trial.

The Adjuvant Program has been funded by the National Institutes of Health (NIH) through advanced design improvements and manufacturing process development. NIH has also funded experiments in a ferret model of avian influenza to evaluate their stockpiled H5N1 vaccine with and without the GVI adjuvant. If successful, we anticipate the NIH may utilize their contractors to help with cGMP manufacture, GLP toxicology testing, investigational new drug (IND) submission to the Food and Drug Administration (FDA), and potentially a Phase I clinical trial funded through NIH.